Influence of trehalose 6,6′-dimycolate (TDM) during mycobacterial infection of bone marrow macrophages
Influence of trehalose 6,6′-dimycolate (TDM) during mycobacterial infection of bone marrow macrophages
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DOI：
10.1099/00221287-148-7-1991
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发表时间：
2002-07-01
期刊：
影响因子：
2.8
通讯作者：
Actor, JK
中科院分区：
文献类型：
--
作者：
Indrigo, J;Hunter, RL;Actor, JK
表面脂类在感染分枝杆菌的天然巨噬细胞反应中的相对作用尚不清楚。海藻糖6，6‘-二聚乙醇酸(TDM)是分枝杆菌细胞壁的主要成分，可引起超敏反应和T细胞非依赖性异物反应。研究了TDM在分枝杆菌感染的原代巨噬细胞反应中的T细胞非依赖性贡献。用天然结核分枝杆菌(MTB)和石油醚脱脂的MTB感染C57BL/6小鼠骨髓来源的巨噬细胞。去除表面脂质会降低巨噬细胞中细菌的存活率，但在肉汤培养中细菌的生长没有损失。细菌与纯化的TDM重组后，巨噬细胞内的细菌存活得以恢复。并对巨噬细胞反应的细胞因子和趋化因子参数进行了研究。IL-1β、TNF-α、IL-6和MIP-1α的产生在脱脂后显著减少，但在TDM重建后恢复。脱脂结核分枝杆菌感染巨噬细胞后，IL-12的产生量显著减少，但IL-10的产生量没有明显减少。此外，脱脂结核分枝杆菌感染后，一氧化氮反应没有受到损害，这表明细胞内存活和巨噬细胞分泌细胞因子和趋化因子受到不同程度的控制。这些研究表明，TDM是天然巨噬细胞对结核分枝杆菌感染的反应的主要组成部分。
The relative role of surface lipids in the innate macrophage response to infection with mycobacteria remains unknown. Trehalose 6,6'-dimycolate (TDM), a major component of the mycobacterial cell wall, can elicit hypersensitive as well as T-cell-independent foreign body responses. The T-cell-independent contribution of TDM to the primary macrophage response to mycobacterial infection was investigated. Bone-marrow-derived macrophages isolated from C57BL/6 mice were infected with native Mycobacterium tuberculosis (MTB) or with MTB delipidated using petroleum ether extraction methods. The removal of surface lipids caused decreased bacterial survival in macrophages, but there was no loss of bacterial growth in broth culture. Bacterial survival within macrophages was restored upon reconstitution of the bacteria with purified TDM. The cytokine and chemokine parameters of the macrophage responses were also investigated. The amounts of IL-1beta, TNF-alpha, IL-6 and MIP-1alpha produced were significantly reduced following delipidation, but were restored upon reconstitution with TDM. The amount of IL-12 produced, but not the amount of IL-10 produced, was also significantly reduced upon macrophage infection with delipidated MTB. Furthermore, nitric oxide responses were not impaired upon infection with delipidated MTB, suggesting that intracellular survival and macrophage secretion of cytokines and chemokines are differentially controlled. These studies indicate that TDM is a major component contributing to the innate macrophage responses to MTB infection.